1. Field of the Invention
The present invention relates to a device with a pump arrangement, with at least one venous catheter, and with at least one arterial catheter, for establishing and maintaining an artificial circulation in a target area of a human or animal body, the artificial circulation being isolated from the blood circulation of the body.
The invention further relates to a method in which an artificial circulation is established and maintained in a target area of a human or animal body, said artificial circulation being isolated from the blood circulation of the body, hereinafter also called the systemic circulation.
2. Related Prior Art
This so-called isolated perfusion of organs or body regions has been used for some time to administer powerful medicaments in the target area and in so doing to avoid their side effects on the rest of the organism, or to administer medicaments at such high concentrations which, if applied systemically, would cause unacceptably severe side effects and incompatibility reactions.
In the context of the present invention, the term “target area” means an organ which can be isolated from the rest of the body in terms of blood circulation, or a body region which can be isolated, for example the extremities, i.e. arms or legs, and the pelvis. A prime example is hyperthermic isolated perfusion with chemotherapeutic substances for treating loco-regional metastases in the arms or legs in cases of malignant melanoma. Other examples include pelvic perfusion in local metastasis of rectal carcinoma, or leg perfusion for dissolution of otherwise treatment-resistant leg-vein thrombosis of the legs. An important area of application of the present invention relates to the last-mentioned thrombolytic perfusion of isolated limbs, predominantly the legs.
To carry out the isolated perfusion, use is made of a pump arrangement with at least one venous catheter and with at least one arterial catheter which are connected to the artery and vein of the target area so that, for a certain time, a small artificial circulation is established and maintained which is separate from the rest of the blood circulation. In order to supply the target area with oxygen in cases where the artificial circulation is maintained for a relatively long period, an oxygenator is also coupled into the artificial circulation, and the carbon dioxide level is also kept constant by means of this oxygenator.
Hitherto, the artery and vein of the target area were therefor surgically exposed, ligatured under direct visual monitoring, and then connected to the arterial catheter and venous catheter respectively. With improved catheterization techniques, it is nowadays also possible to perform an isolated perfusion from outside just by puncturing the vessels, i.e. without an operation, a separation being effected between the artificial circulation and the systemic circulation.
In “Double-balloon catheter for isolated liver perfusion: an experimental study. Cardiovasc. Intervent. Radiol. 2001; 24: 191-193, Cwikiel et al. report on the isolated perfusion of a pig liver with four catheters. The catheters used sealed off the vessels, in which they lay, with the aid of a balloon fixed to them.
The artificial circulation in the target area can thus be separated from the systemic circulation in the rest of the human or animal body surgically, with the aid of catheters, or alternatively by ligaturing, etc.
Particularly when the isolated perfusion involves powerful but toxic medicaments, care must be taken to ensure that the isolated artificial circulation functions in isolation from the rest of the systemic circulation and that leakage of medicaments into the blood circulation is avoided, in order to ensure that the administered medicaments cannot affect the rest of the body.
However, it is often impossible to completely prevent atypical vessel courses or exits, venous plexuses or lymph tracts either surgically or by catheterization, with the result that there may be continuous exchange of blood between the artificial circulation and the blood circulation of the body.
In order to minimize this risk of leakage, a pressure drop is avoided on the venous side between the two circulations. If the pressure in the isolated artificial circulation is too low, blood flows from the systemic circulation into the treated target area, so that the blood volume circulating in the artificial circulation increases. However, the reverse scenario is of greater disadvantage, that is to say when the pressure in the artificial circulation is too high. Then, blood which contains the administered medicaments is forced into the blood circulation of the rest of the body.
It will be evident from the above that, in the context of isolated perfusion, reliable control of leakage is extremely important. In addition to guaranteeing a constant system volume on the side of the artificial circulation, leakage control has hitherto been done with the aid of radioactive substances. In “Quantitative radionuclide leakage control during isolated limb perfusion”, Nuklearmedizin 1994; 33: 248-253, Sprenger et al. describe a twin indicator technique which uses albumin labeled with two different isotopes. The first albumin preparation is delivered to the blood circulation of the body, in order to monitor the position of the measurement probe over the heart. Slipping of the measurement probe causes a change in the signal from the measurement probe. The second albumin preparation is divided in a defined ratio between the artificial circulation and the blood circulation of the body (hereinafter also called the systemic circulation). As long as the measurement probe over the heart records a constant ratio between the first and second albumin preparations, the artificial circulation is reliably isolated from the systemic circulation. If the ratio changes, this points to a leakage.
If a leakage which has been detected in this way cannot be rectified by changing the pressure ratios, the isolated perfusion is discontinued and administration of the medicament is stopped or is not even started.
A disadvantage of the twin indicator technique, apart from the patient's exposure to radiation, is the particular effort associated with using radioactive material, in particular the requirements placed on personnel, structural measures, handling of radioactive waste, etc. Moreover, leakage via the lymph flow cannot be detected when using labeled albumin.
A further disadvantage of the twin indicator technique lies in the associated high costs arising from the expenditure in terms of technology and equipment, the personnel requirements, and the structural measures prescribed by law.
However, since isolated perfusion by catheterization can, apart from leakage control, be carried out without difficulty even in small clinics, there is a need for a simpler method of leakage control and for corresponding devices for carrying out the method.